A Schmidt rearrangement-mediated synthesis of novel tetrahydro-benzo[1,4]diazepin-5-ones as potential anticancer and antiprotozoal agents

European Journal of Medicinal Chemistry
Daniel InsuastyRodrigo Abonia

Abstract

Novel tetrahydro-5H-benzo[e][1,4]diazepin-5-ones, several of them, containing the quinoline pharmacophore, were synthesized via a Schmidt rearrangement from their corresponding 1,2,3,4-tetrahydro-4-quinolones mediated by the NaN3/H2SO4 reaction conditions. Twelve of the obtained compounds were in vitro screened by the US National Cancer Institute (NCI) for their ability to inhibit 60 different human tumor cell lines, where compound 24a presented a remarkable activity against 58 of the 60 cancer cell lines, with the most important GI50 values ranging from 0.047 to 8.16 μM and LC50 values ranging from 9.4 to > 100 μM. Additionally, some of them were evaluated as antimalarial, antitrypanosomal and antileishmanial agents. The best antimalarial response was observed for compound 22g with an EC50 = 13.61 μg/mL for Plasmodium falciparum, while compound 24d exhibited high activity against Trypanosoma cruzi. and Leishmania (V) panamensis with EC50 = 2.78 μg/mL and 3.35 μg/mL respectively.

Citations

Jul 16, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Susiany P LopesDamião P de Sousa
Nov 24, 2019·Bioorganic Chemistry·Marcela VettorazziRicardo D Enriz
Feb 24, 2021·Bioorganic Chemistry·Pratibha Yadav, Kamal Shah

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